Amy is aroused by Penny's ex-boyfriend Zack Johnson and is unfamiliar with the feeling. Sheldon thinks she has contracted an alien parasite. Meanwhile, Howard and Raj battle out who is the hero and who is the sidekick in their friendship.
While eating their take-out dinner around the coffee table, Sheldon complains that the next person who ate with their mouth full will be put to death. This comment is followed later by Sheldon asking what everyone thought the best number was. Not 5,318,008, as suggested by Raj, since upside-down on a calculator it spells “Boobies”. Sheldon explains that the best number is 73 partly because it's a prime number. The other part basically has to do with the fact that 7*3 is 21 and 2+1 = 3 (another prime number).
Amy, Bernadette and Penny are spending their night out together at a bar. Bernadette loves the heart-shaped locket Howard gave her after yet another night of enduring his mother. Amy provides a factoid that the iconic Valentine's heart shape is not based on a human heart, but rather the shape of the buttocks of a female bending over. Penny’s ex-boyfriend, Zack, stops by to drop off menus, and stops by the ladies saying "hi". Actually, Amy let’s out an involuntary “Hoo!” a couple of times, including when Zack bent over to pick up a box. Penny knows what is bothering Amy, but she misses that she is aroused.
Howard and Raj find out a lab tech got bitten by a rat that was injected with radioactive isotopes. They wonder which of them would be the better Rat-man and which could be his sidekick. Leonard is unhappy at still being at the nerds' table.
Amy is slicing up pieces of a human brain and having lunch with Sheldon. They try to analyze the symptoms she had the previous night. Raised temperature, sweaty palms, and vascular throbbing in her ears and genitalia. Sheldon reduces the causes to hyperthyroidism, premature menopause, an alien parasite, or sexual arousal. Amy eliminates hyperthyroidism & menopause. Amy and Sheldon must face the cold, harsh truth that she was sexually aroused by Penny's friend, Zack. Sheldon prefers the alien parasite hypothesis. To handle her condition, he suggests Star Trek and the teachings of the Vulcan way of Kolinahr. Amy wonders why she should use advice from some cheap science fiction show. Sheldon uses Kolinahr to suppress his anger at Amy and then leaves accidentally mistaking her brain slices for his lunch.
Howard wants the sidekick argument with Raj settled, so he puts a giant spider in a large jar and wants both of them to put one hand in the jar. First one to pull out his hand is destined to be the sidekick. Raj put his hand in and smiles because the spider was crawling up Howard's arm. Next they decide on a wrestling contest. Leonard is the judge as they spend the whole night circling and trash-talking each other.
Sheldon heads down to do laundry and runs into Penny. He starts to talk about this relationship with Amy which he thought was a purely intellectual one. She has changed and had become a slave to her baser urges...like Penny. Penny asks what the right scientific word was. Sheldon replies, “Forget science; she's horny.” Penny tells Sheldon that he can help her with those urges. (It's illegal to spay a human being!") Then he jumps to a conclusion and figures he might as well get it over with. Penny thinks Sheldon going to satisfy Amy himself, but he decides to get Zack to do it.
Zack meets them in the same bar and Amy approaches him saying, “I stand here before you, 130 pounds of raging estrogen, longing to grab your hold of your gluteus maximus and make Shakespeare's metaphorical Beast with Two Backs.” Zack is confused as usual. (My gluteus what?) Based upon his ape-like expression, she decide to start using Vulcan disciplinary practice of Kolinahr for her urges, though there is one more “Hoo!” before she leaves. Outside the bar, she does try holding Sheldon's hand though doesn’t feel anything.
- Guest starring:
- Teleplay: Lee Aronsohn, Jim Reynolds & Maria Ferrari
- Story: Chuck Lorre, Steven Molaro & Steve Holland
- The TV Critic: "The writers continue to use Amy to deal with Sheldon plots which they realize are too valuable to use up right now. So instead of Sheldon feeling his first stirrings of sexuality we substitute Amy. I think it's a good idea in the sense that The Big Bang Theory is going to run for the foreseeable future so why blow through Sheldon stories when we can test them on surrogate Sheldon first. Sheldon actually turns out to be a good friend, going to great lengths to satisfy Amy's urges even if it means losing respect for her...The Amy-Sheldon relationship is still something I enjoy exploring even if the writers never figure out quite how to pitch her. The rest was poor filler." 
- The A.V. Club gave this episode a C+.
- IMDb user reviews
- Title Reference: The title refers to one of Sheldon's diagnosis about why Amy had her symptoms.
- Chuck Lorre's vanity card.
- This episode was watched by 12.03 million people with a rating of 3.9 (adults 18-49).
- This episode aired in Canada on December 9, 2010 with 2.659 million viewers and a weekly ranking of #3.
- In the United Kingdom, this episode aired on January 6, 2011 with 1.192 million total viewer and a weekly ranking of #17.
- Episode transcript 
- Sheldon wears his red Robot Evolution shirt.
- Bernadette is only seen in one scene of this episode and Penny is only seen in two scenes of this episode.
- Mayim Bialik's second episode as a main cast member since her absent appearance in the previous episode (S4E9).
- Howard states, "I’m legally obligated to inform you that I took a karate lesson when I was 11. I’d be a regular ninja by now if my mom could’ve arranged a carpool." In "The Jiminy Conjecture" (S3E2), he similarly revealed, "Don’t push me, Sheldon. I may be small, but I took kung fu when I was 13, and I remember a good deal of it."
- In real life, Howard's actor, Simon Helberg, studied karate during his youth, having earned his black belt at age 10.
- Rajesh and Howard argue superhero names Rat-Man, Mouse-Boy and Kid Vermin for themselves if one was bitten by a radioactive rat in a lab. Akin to this, in "The Hot Troll Deviation" (S4E4), Rajesh said if Sheldon's superpower were arrogance, his name would be Captain Arrogant, while Sheldon contended his name would be Dr. Arroganto.
- First contest in a gym, with the second occurring in "The Rothman Disintegration" (S5E17).
- Sheldon shows his favorite character Spock's salute (from Star Trek).
- In "The Lunar Excitation" (S3E23), Amy said, "I don’t object to the concept of a deity, but I’m baffled by the notion of one that takes attendance." Amy suggests religion, in the episode of this article, when Sheldon says, "You know, in difficult moments like this, I often turn to a force greater than myself." This reaffirms she does not object to religious beliefs.
- While speaking to Zack, Sheldon makes a reference to "The Justice League Recombination" (S4E11): "Good grief. It’s like trying to talk to a dolphin."
- Sheldon and Amy's discussion of her physiological reactions (HOO!) to Zack is an homage to Abbott and Costello's famous "Who's on First?" routine.
- First time that, unlike Sheldon, Amy shows that she has sexual arousal.
- "Lupus" on diagnosis board may refer to the TV series "House, M.D."
- Sheldon considers 73 the best number, coincidentally the episode number of this episode.
- Amy's exposure to Penny has a greater effect on her and her sexually than Penny's effect on Sheldon.
- Rat-Man is the main character of an Italian comic book series.
- The fast food restaurant Quiznos was referred to. One of their ads featured Jim Parsons. Bernadette competed in a Miss Quiznos beauty pageant in 1999 in "The Troll Manifestation".
- Rajesh and Howard argue with each other against being considered a sidekick. Simon Helberg had previously appeared as a supervillain's sidekick in the web original Dr. Horrible's Sing-Along Blog.
- Leonard: We get it! 73 is the Chuck Norris of numbers.
- Sheldon: Chuck Norris wishes.
- Howard: Let me ask you a question. What are you most afraid of?
- Raj: I don't know. Nuclear war. Accidentally being buried alive. Any of those movies where you get a phone call that says you're going to die, and then you do.
- Amy: HOO! (Often repeated)
- Amy: Penny's friend, Zack, stopped by and said "hello" and I said "hoo!"
- Sheldon: Hoo?
- Amy: Zack.
- Sheldon: Then why did you ask?
- Amy: Ask what?
- Sheldon: Who?
- Amy: Zack.
- Sheldon: All right, let's start over. What did you say when Zack walked in?
- Amy: Hoo!
- Sheldon: Zack.
- Amy: Why do you keep saying 'Zack'?
- Sheldon: Because you keep saying 'Who'.
- Amy: I'm not saying 'hoo' now. I said 'hoo' last night.
- Sheldon: And the answer was Zack, correct?
- Amy: There was no question; I simply said "Hoo!"
- Sheldon: [short pause] All right. I think I have enough to go on.
- Amy: Sheldon, I am not going through menopause!
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